The basic goal of this research program is to determine the mechanism of cytotoxicity of elevated levels of carbohydates. In classical galactosemia (hexose-1-phosphate uridylyl transferase, EC 2.7.7.12, deficiency) elevated galactose levels may severely inhibit the metabolic and functional activities of phagocytic cells. From these studies, we hope to gain further insight into the bioenergetics of phagocytosis and bactericidal function of polymorphonuclear leukocytes. The metabolic disposition of galactose will be the focus of continued efforts in this laboratory. Extending our information of galactose cytotoxicity, the analogous injury to tissues by glucose in the diabetic animal will be explored. A major thrust of this research program will include expansion in the area of the discovery in this laboratory that migration of lysosomal enzymes to the nuclei of rat liver may be associated with the induction of enzymes of lipogenesis. This finding has stimulated current efforts to uncover possible mechanisms for lysosomal interaction in the process of the stimulation of chromatin and m-RNA synthesis activities.